Jardiance Label Claim Is The Next Milestone For Booming SGLT2 Class

After a humble launch four years ago mired in safety concerns, the SGLT2 inhibitors have quickly blossomed into an important treatment option for diabetics. This status will only be confirmed should Jardiance achieve the first cardiovascular claim for a diabetes drug – an FDA panel hearing next week will convene to discuss this.

Consensus forecasts reveal that great things are already expected – EvaluatePharma data show the SGLT2s becoming the third-biggest diabetes class in 2022, contributing two of the five biggest-selling brands that year (see tables below). It is unclear to what extent these high hopes are based on Jardiance winning a distinct indication describing a reduction in cardiovascular death. The drug’s makers reckon that it is well within their grasp.

The EMPA-REG outcome study showed a 14% reduction in the risk of cardiac events, the primary endpoint of the trial, which was a composite of three measures. This included cardiovascular death, which showed an impressive 38% risk reduction; it is this measure in particular that Lilly (NYSE:LLY) reckons will help it achieve a label claim (EASD – Lilly blooms with full Jardiance outcomes data, September 18, 2015).

Others are not so sure. Analysts at Leerink, for example, believe that while the data will definitely be incorporated into the clinical data section, a distinct indication would be a surprise. The trial failed to hit a secondary composite endpoint that incorporated an additional measure, and as such any claims would be based on “admittedly robust but unfortunately exploratory endpoints.”

This is certainly something the FDA might be reluctant to sanction, in terms of setting a precedent, and will no doubt be a focus for discussion at the panel hearing, scheduled for June 28. Briefing notes due later this week will also give an insight into the regulator’s thinking.

Guideline boost

Whether or not a label claim will allow Lilly and its partner Boehringer Ingelheim to start aggressively marketing a cardiac benefit, treatment guidelines will also soon reflect the study’s results. This should also help drive demand for the drug, and possibly the whole SGLT2 class.

However, negative findings are afflicting the other agents in this class: Johnson & Johnson’s (NYSE:JNJ) Invokana and AstraZeneca’s (NYSE:AZN) Farxiga both have had stronger warnings about acute kidney injury added to their US labels.

Jardiance seems to be fast pulling away from the competitors on both safety and efficacy. With outcome studies for the others some years away, the product should be able to dominate its segment of the market.

Despite all this, sellside forecasts still show J&J’s Invokana remaining a huge product. Being first to market has no doubt helped, and the Jardiance launch has disappointed some – although this could all change in the coming months.

Overall the future of the SGLT2 class looks highly promising, and the table above shows that both Jardiance and Invokana have had around $1bn in sales added to their 2020 forecasts over the past 12 months.

The SGLT2s have a number of things going for them: the convenience of a pill, a marginally bigger impact on blood sugar levels than the older DPP-IV class and, perhaps more importantly, the absence of the cardiovascular safety signal that has marred certain DPP-IV drugs (Januvia's surprising all clear, courtesy of Tecos, April 28, 2015).

So it is perhaps not surprising that the class as a whole is projected to be worth more in sales than the DPP-IVs come 2022, as the table below shows.

The cardiovascular outcomes study for Invokana should yield data next year, while Farxiga's is due later in 2019, and both will help determine whether SGLT2s can be considered cardio-protective. Given the diverging clinical data, there seems to be a high probability that this is something for only Jardiance to boast.